期刊
CELL RESEARCH
卷 26, 期 2, 页码 206-216出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/cr.2016.6
关键词
acute liver failure; functional hepatocytes; bioartificial liver
类别
资金
- Strategic Priority Research Program of CAS [XDA01030601, XDA01030602]
- National Natural Science Foundation of China (NSFC) [31225016, 91319307, 81471948]
- Ministry of Science and Technology of China (MOST) [2013CB967103, 2012CB945001]
- Science and Technology Commission of Shanghai Municipality (STCSM) [14XD1404200, 15JC1400200]
- NSFC [81170418, 81302836]
- Natural Science Foundation of Jiangsu Province [BK20131084]
- MOST [2013AA032202]
- Fudan Foundation [2013ZSQN28]
- STCSM [14YF1406900]
Acute liver failure (ALF) is a life-threatening illness. The extracorporeal cell-based bioartificial liver (BAL) system could bridge liver transplantation and facilitate liver regeneration for ALF patients by providing metabolic detoxification and synthetic functions. Previous BAL systems, based on hepatoma cells and non-human hepatocytes, achieved limited clinical advances, largely due to poor hepatic functions, cumbersome preparation or safety concerns of these cells. We previously generated human functional hepatocytes by lineage conversion (hiHeps). Here, by improving functional maturity of hiHeps and producing hiHeps at clinical scales (3 billion cells), we developed a hiHep-based BAL system (hiHep-BAL). In a porcine ALF model, hiHep-BAL treatment restored liver functions, corrected blood levels of ammonia and bilirubin, and prolonged survival. Importantly, human albumin and alpha-1-antitrypsin were detectable in hiHep-BAL-treated ALF pigs. Moreover, hiHep-BAL treatment led to attenuated liver damage, resolved inflammation and enhanced liver regeneration. Our findings indicate a promising clinical application of the hiHep-BAL system.
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